Electrophysiological experiments using intracellular recording techniques and extracellular pharmacologic applications have been performed on mouse spinal neurons and pituitary cells grown in tissue culture and on molluscan central neurons. The research has focussed on the the mechanisms of how endogenous and exogenous ligands alter neuronal excitability. We have found that endogenous substances and exogenous drugs can produce superficially similar effects on cultured neurons. We have applied "fluctuation" and patch clamp analysis to one of the actions of transmitters and drugs and find that both natural and synthetic agents can open two-state C1- ion channels. We have begun to characterize other forms of chemical excitability revealed by pharmacological applications of these substances. We plan to examine the hypothesis that some pharmacologic actions of certain drugs are mediated through receptors for endogenous ligands.